Transfusion Medicine Justine A. Lee, DVM, DACVECC, DABT Garret Pachtinger, VMD, DACVECC CEO, VetGirl COO, VetGirl Justine@vetgirlontherun.com Garret@vetgirlontherun.com

Copyright 2014 © VetGirl, LLC

Introduction

Justine A. Lee, DVM, DACVECC, DABT

CEO, VetGirl

Dr. Lee’s financial disclosure

Introduction

Garret Pachtinger, VMD, DACVECC

COO, VetGirl

Sponsorship

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Why transfuse?

!  Underlying causes of anemia: !  Blood loss !  Hemolysis !  Decreased production

!  Why is anemia significant? !  Decreased O2 delivery to tissues (DO2)

Oxygen content: CaO2

CaO2 = [1.34 X Hg X SaO2] + 0.003 X PaO2

! Does your IMHA patient need blood or oxygen? ! SaO2 = 100% ! PaO2 = 100% ! HCT = 12%

Transfusion trigger

Transfusion trigger*

!  HCT !  Human: 25% vs. Veterinary: 20%

!  Chronicity

!  Normovolemia

!  Rate of ongoing losses

Clinical signs

!  Clinical signs? !  Tachycardiac !  Tachypneic !  Hypotension unresponsive to IVF !  Hypovolemic shock !  Pulse quality !  Pallor

Feline In-house blood donors !  Healthy !  Indoor only! !  No exposure to other cats! !  >10# !  Large/lean !  1-7 yo !  UTD !  FELV/FIV !  Blood type

!  CBC !  CHEM !  UA !  T4 !  Fecal !  Toxoplasma gondii !  Mycoplasma

(Haemobartonella) !  Bartonella spp !  Heartworm !  Blood type !  FIP?

Canine In-house blood donors !  > 1 year !  Healthy !  > 25 kg !  UTD !  No concurrent meds !  Preventative meds

!  Good temperament !  Physical exam !  CBC !  Chemistry !  UA !  Tick titers !  E. canis/equi !  B.canis/gibsonii !  Heartworm !  Blood type

Download the ACVIM Consensus free!

Canine blood typing

!  13 different blood types

!  Dog Erythrocyte Antigen (DEA) 1.1, 1.2, 3,4,5,7

!  DEA 1.1, 1.2, and 7: most antigenic

!  DEA 1.1 more immunogenic than 1.2 !  Very antigenic !  Positive: has antigen on RBC surface !  Negative: antigen missing on surface

Universal Donor

! True universal donor: (-) for all but DEA 4+

! Most universal donors: DEA 1.1, 1.2, 7 (-)

! New blood type �Dal� ! Dal may be missing in an unknown proportion of

Dalmatians

Canine blood typing

Percentage %

Blood types Positive Negative DEA 1.1 1.1 (A1) 33-45 55-67

1.2 (A2) 7-20 35-60 DEA 3B 5-10 90-95 DEA 4C 87-98 2-12 DEA 5D 12-22 78-88 DEA 7Tr 8-45 55-92

DEA 1.1 negative

! DEA 1.1 (-) can be given to (-) or (+)

! Universal donor

! Use when medical conditions preclude testing

! Hypovolemic or hemorrhagic shock !  IMHA ! autoagglutination

DEA 1.1 positive

! Highly antigenic

! Can still use as blood donors

! Use for 1.1 + dogs ONLY!

!  �Waste� + units for + dogs

Feline blood type groups !  A, B, AB, �Mik� !  Type A more common

!  Type B strong anti-A antibodies # fatal transfusion reaction! *B students don�t like A students*

!  Type A weak anti-B antibodies # shortened half life of RBC (2 days vs. 29-39 days)

Feline blood typing Percentage%

Percentage%

Type A Type B Type A Type B Abyssinian 86 14 Himalayan 93 7

Birman & Somali

84 16 Japanese Bobtail

84 16

British Shorthair

60 40 Maine Coon 98 2

Burmese 100 0 Nor. Forest 93 7

Cornish Rex 66 34 Persian 84 14

Devon Rex 59 41 Scottish Fold

82 18

DSHA XX XX Siamese/ Tonkinese

100 0

Percentage (%) Percentage (%)

Domestic shorthair* Type A Type B Purebred cats Type A Type B

USA Northeast 99.7 0.3 Abyssinian 84 16

North Central

99.6 0.4 Am. shorthair

100 0

Southeast 98.5 1.5 Birman* 82 18

Southwest 97.5 2.5 British shorthair*

64 36

West Coast 95.3 4.7 Burmese 100 0

Blood compatibility

!  Pre-transfusion testing ! Prior to infusion of donor products

!  Testing of donor

!  Selection of appropriate donor units ! Blood type ! Blood crossmatching

Blood typing cards

!  In-practice blood typing kit !  Based on agglutination reaction that occurs when rbc which

contain DEA 1.1 antigen on their surface interact with a murine monoclonal antibody specific to DEA 1.1

!  Laboratory gel-test DMS Laboratories 2 Darts Mill Road Flemington, NJ 08822 1-800-567-4367

Blood Typing: Canine

DEA 1.1 -

DEA 1.1 +

DEA 1.2 +

DEA 1.1 +

Type A

Type AB

Type B

Feline blood typing

Blood crossmatching !  Detects serological incompatibility by identifying

antibodies in donor or recipient plasma against recipient or donor RBCs.

!  Major* vs. minor crossmatch !  MAJOR: patient plasma with donor RBC !  MINOR: donor plasma with patient RBC

* More important to determining survival of transfused RBCs

Crossmatching

!  Autocontrol (recipient RBC + plasma): rules out autoagglutination

!  Any hemolysis or agglutination in major or minor = incompatibility

!  Minor BCM – should be compatible in dogs but is of lesser significance in that canine donor plasma should not contain significant antibodies.

Crossmatching

!  Dogs lack significant naturally occurring alloantibodies # can be safely transfused without a BCM prior to the 1st transfusion!

!  4-7 days to develop antibodies!

Crossmatching

! Since cats have naturally occurring alloantibodies and may experience a severe reaction to their first transfusion, a BCM should be performed prior if blood typing is not available.

Crossmatching Technique

So what now?

! Consider using blood typing cards for patients receiving acute transfusions (i.e., hemoabdomen, trauma)

! Consider CM when multiple transfusions will be given over one week (i.e., IMHA)

! Consider blood typing cards for FFP use

PRESERVING BLOOD

Anticoagulant preservatives

!  Goal: !  Maintain rbc viability !  Lengthen survival of rbcs post-transfusion !  Am Assoc Blood Bank (AABB) standards: 75% of RBC

must survive > 24 hours to be acceptable and successful.

!  Longer storage: viability decreases

Anticoagulant preservatives

!  CPDA-1 (Citrate-Phosphate-Dextrose-Adenine) !  RBC 2,3-DPG & ATP better maintained !  Good anticoagulant-preservative solution !  WB: stored 28 days !  Canine pRBC: 21 days !  Ratio: 1 ml CPDA-1 to 7-9 ml blood

Anticoagulant preservatives !  CPD (Citrate-Phosphate-Dextrose)

!  pRBC: 21 days !  Ratio: 1 ml CPD1 to 7-9 ml blood

!  ACD (Acid-Citrate-Dextrose) !  pRBC: 21 days (dogs and cats) !  Ratio: 1 ml ACD to 7-9 ml blood

Anticoagulant preservatives !  Heparin

! Not generally recommended! ! 625 U/50 mls whole blood

!  Additive Solutions (i.e., Adsol, Nutricel, Optisol) ! Protein-free solution added to red blood cells

after plasma removed from unit of WB ! pRBC: 28 days (canine)

Goals of fluid therapy !  Increase oxygen delivery !  Increase & maintain organ tissue perfusion !  Maintain blood pressure !  Maintain euvolemic state !  Correct electrolyte or acid-base imbalances !  Treat for hypoproteinemia

Blood products

! Packed red blood cells (pRBC) ! Provides: RBC

! HCT = 80% ! Minimal COP! ! 10-20 ml/kg will raise PCV 10-20% ! Treatment for anemia ! No clotting factors ! Can reconstitute with 0.9% NaCl ! Store at 1-6 C for 28-35 days

! Equation:

ml blood = PCV(target) – PCV(recipient) 80 ml/kg x BW (kg) PCV (donor)

!  10-20 ml/kg ! pRBCs ! FFP ! FP

Dose: pRBCs

Blood products ! FFP

! Separated from whole blood and frozen at -20 to -30 within 6-8 hours of collection

! Provides: plasma, albumin, all coagulation factors (labile, Vit K dept), alpha-macroglobulins

! COP = 20

! Storage: 1 year frozen at -20°C or below

! 10-20 ml/kg

Blood products

! FFP ! Dose: 6-20 ml/kg for coagulopathies

! Dose for albumin: 45 ml/kg increases albumin by 1 g/dl

! 30 kg retriever: 1.3 liters (5-6 units)

! Minimal albumin!!!

Blood products

! FFP ! Dose: 6-20 ml/kg for coagulopathies

! Dose for albumin: 45 ml/kg increases albumin by 1 g/dl

! 30 kg retriever: 1.3 liters (5-6 units)

! Minimal albumin!!!

Blood products !  Frozen plasma (FP)

! Provides: plasma, albumin, stable coagulation factors (Vitamin K dept: II, VII, IX, X)

! COP = 20

! 10-20 ml/kg

! Collected > 6-8 hours from whole blood

! Storage: 5 years frozen at -20C (1 year as FFP, 4 years as FP)

! �Waste� on Vit K deficiency patients!

Blood products !  Fresh Whole blood (FWB)

! Provides: RBC, plasma proteins, COP 20, all clotting factors, WBC

! Platelets (limited)

! HCT: 40%

! 20 ml/kg will raise PCV 10%

! Shelf life: < 8 hours

! Preparation: Use immediately!

Blood products

!  Stored Whole blood (SWB) ! Provides: RBC, WBC, Plasma proteins

! Platelets only viable for 2 hours after refrigeration

! Labile coag factors (V, VIII) viable for 24 hrs

! HCT = 40%

! Defined: > 8 hours old and up to 30 days (if using CPDA-1 collection bags)

Blood products

! Platelet rich plasma and plasma concentrates ! Provides: Platelets, few RBC and WBC

! Some plasma

! Shelf life: 5 days at 22°C

!  Intermittent agitation necessary

! Administer following collection and preparation (sit undisturbed for 30 min after harvesting)

!  Lyophilized platelets !  Davidow et al, JVECC 2012

!  Fresh platelets vs. lyophilized platelets !  No significant change in platelet count with either

product

Platelet Concentrates

Blood products

! Cryoprecipitate (CRYO) ! Provides: concentration of VIII, vWF, XI, XIII,

fibrinogen, fibronectin

! Prepared from FFP, which is thawed at 0-6C # precipitate: cryo

! 12 months frozen at -20C

! Dose: 1 unit/10 kg

HBOCs: Oxyglobin

! Oxyglobin ! Ultrapurified ! Bovine ! Stroma free ! LRS base ! Used for treatment of anemia ! 10-30 ml/kg (not to exceed 10 ml/kg/hr) ! 10 ml/kg in dogs will raise Hg 2 g/dl = PCV 6%

HBOCs: Oxyglobin ! HBOCs

! COP 40 ! Fluid overload ! Pigmentation

changes

! $$ ! Good storage !  Interferes with

colometric testing

Protocol for transfusions: !  Evaluate the unit

!  Use a filter

!  Pick which catheter you give it through

!  Pre-treat? !  Diphenhydramine 0.5 mg/kg SQ or IM !  DexSP 0.1 mg/kg IV

Protocol for transfusions: ! Rate dependent on status

! Heart disease: < 4 ml/kg/hr

!  If stable and normovolemic: ! 0.25-0.5 ml/kg for 30 minutes !  If no reaction, increase to 0.5 ml/kg (prbc or

WB) or 2-6 ml/kg (FFP)

Protocol for transfusions: ! Monitor for transfusion reaction

! TPR q 1-5 minutes initially, then q. 15 minutes until finished.

!  If reaction: ! Treat ! Slow down the transfusion ! Discontinue

AUTOTRANSFUSIONS

Autotransfusions

! When can we autotransfuse?

! VetGirl’s rule: From the chest! ! Dirty, dirty abdomen

!  Is the blood sterile? !  Is the blood free of neoplasia? !  Is it end-stage disease?

TRANSFUSION REACTIONS

Autotransfusions

! Sterile collection of blood (60 mls syringes) ! Filter ! Give back IV via filter ! No need to add preservative

! Hypocalcemia

Transfusion reactions

!  Immune-mediated ! Hemolytic

! Acute (pre-existing alloantibodies or prior sensitization)

!  Hemolytic reactions: Fever, tachycardia, weakness, muscle tremors, vomiting, collapse, hemoglobinemia, hemoglobinuria

!  Due to: mismatched transfusion !  Nonhemolytic reactions: urticaria, pruritus, pyrexia, vomiting

!  Due to: antibodies to WBC, plt, plasma protein !  Transient

! Delayed (4-21 days post-transfusion)

Transfusion reactions ! Nonimmune-mediated

! Trauma to the rbc: ! Overheating (protein denaturation, increased

bacterial growth) ! Freezing of rbc ! Mixing rbc with non-isotonic solutions ! Warming and then rechilling ! Collecting or infusing blood through small needles or

catheters

Transfusion reactions ! Nonimmune-mediated

! Bacterial pyrogens and sepsis (improperly collected and stored blood)

! Dark brown to black supernatant plasma: digested hemoglobin from bacterial growth

! Citrate intoxication: hypocalcemia

Risks of blood transfusion medicine !  Veterinary medicine reactions: 3%

!  Risks: !  Disease transmission (FIP, Leishmania) !  Elyte and acid-base disturbances (hypocalcemia) !  ALI !  Microembolic disease !  Coagulopathy !  Immunosuppressive effects*

!  6X more nosocomial infection !  More sensitive marker of injury severity?

!  Hemolytic transfusion reactions (HTR) !  Allergic/anaphylactic reactions (ATR) !  Febrile, nonhemolytic reactions (FNHTR)

!  Transfusion-transmitted infections (TTI) !  Transfusion-related acute lung injury (TRALI) !  Transfusion-associated circulatory overlaod

(TACO)

Transfusion Reactions

!  AlloAB against RBC antigen

!  Hemolytic serum

!  Hemoglobinuria

!  Elevation in body temp

!  Vomiting

Hemolytic Transfusion Reactions

! Histamine release ! Treat with diphenydramine ! Vomiting, facial swelling, hives, elevated

body temperature

Allergic/Anaphylactic Reactions

!  Increase in at least 2� in body temperature during transfusion

!  No signs of hemolysis

!  Usually due to cellular components (WBCs, platelets, other) !  Leukoreduction

!  Usually resolves without intervention !  Slow transfusion rate

Febrile, Non-hemolytic Reactions

!  Transfusion-transmitted infections !  Reports in the veterinary literature

!  Transfusion-related acute lung injury !  Pulmonary edema/pulmonary vasculitis

!  During or within 6 hrs transfusion !  Massive transfusion

!  1 blood vol < 24 hrs, ½ blood vol < 3 hrs, 150% blood vol !  Immune-mediated !  Diuretics not indicated !  No reported cases in veterinary literature

!  Transfusion-associated cardiovascular overload !  Hydrostatic pulmonary edema (treat with diuretics)

TTI, TRALI, TACO

CASE EXAMPLES

�Buffy,� 4 yo FS Cocker, 10 kgs

Presenting complaint: ! O noticed the following clinical signs:

! Orange urine ! Lethargy ! Vomited once this week ! Anorexia for 2 days

Buffy�s initial exam

!  T: 104.8° F (40.4° C) !  HR: 180 !  Panting !  Bounding pulses !  Pallor !  Icterus !  2/6 heart murmur !  10 kgs

Buffy�s Big 4/SAG ! Tells you all you need to know in < 1 minute!

! PCV 15%/TS 7 g/dL

!  Icteric & hemolyzed serum

! BUN 5-15 mg/dL

! Blood glucose 170 mg/dL

Goal #1: Perfusion, perfusion, perfusion

! Start with crystalloids first ! Cheap $ ! Life-saving ! 20-30 ml/kg IV balanced crystalloid over 20

minutes ! Perfusion – keep on IVF!

Goal #1: Perfusion, perfusion, perfusion

! Check perfusion values !  If still unstable, re-bolus as needed:

! 10-20 ml/kg IV crystalloids/20 minutes ! 5 ml/kg HES IV/20 minutes

Back to Buffy – does she need fluids?

!  T: 104.8° F (40.4° C) !  HR: 180 !  Panting !  Bounding pulses !  Pallor !  Icterus !  2/6 heart murmur !  10 kgs

Back to Buffy – does she need fluids?

!  10 kgs, HR 180, pallor

! Bolus 200 mls of crystalloid over 20-30 minutes

! Recheck HR, pulse quality

! HR 160 bpm, bounding pulses

Back to Buffy – does she need fluids?

!  Rebolus 100-200 mls of crystalloid again!

!  Recheck HR, pulse quality

!  HR 150 bpm still. Next?

!  Bolus 50 mls of HES over 30 minutes!

!  HR 120 bpm

Oxygen content = CaO2

! CaO2= Hgb X 1.34 X SaO2 + (0.003 X paO2)

!  i.e. IMHA with a PCV of 9% ! Does it need RBC or O2?

! Does Buffy need blood or oxygen?

Give Buffy a blood transfusion! !  Pros vs. cons of giving antigenic RBC

!  Deliver oxygen! !  Stimulate immune system?

!  What type should I give? !  Universal donor (A-/DEA 1.1)

!  Choices:

!  PRBC !  FRESH whole blood !  FFP? !  Oxyglobin

PRBC

! What�s in it? RBC only! Perfect!

! Unable to blood type

!  10-20 ml/kg over 1-4 hours, depending on how stable.

Fresh whole blood !  Readily available at your clinic!

!  Provides: RBC, plasma proteins, all clotting factors, WBC, some platelets, PCV 40%

!  Shelf life: < 8 hours

!  Preparation: Use immediately!

!  20 ml/kg will raise PCV 10%

Fresh Frozen Plasma (FFP)

!  What�s in it: Plasma, albumin, all coagulation factors (Vit K dependent factors, labile coagulation factors), and alpha-macroglobulins

!  Does Buffy need it? NO!

!  10-20 ml/kg

Where do we go from here?

References:

!  Canine and Feline Blood Donor Screening for Infectious Disease Wardrop KJ, Reine NJ, Birkenheuer B, et al. J Vet Intern Med 19[1]:135-142 Jan-Feb'05 ACVIM Consensus Statement

!  Clinical Use of Blood Products in Cats: A Retrospective Study (1997-2000). Castellanos I, Couto CG, Gray TL. J Vet Intern Med 2004;18[4]:529-532.

!  Red blood cell transfusions in cats: 126 cases (1999). Klaser DA, Reine NJ, Hohenhaus AE. J Am Vet Med Assoc 2005;226(6):920-923.

!  Whole Blood Transfusions In 91 Cats: A Clinical Evaluation

J Feline Med Surg 6[3]:139-148 Jun'04 Retrospective Study 27 Refs C. Weingart, U. Giger, B. Kohn *

!  Massive transfusions in dogs: 15 cases (1997-2001) Jutkowitz LA, Rozanski EA, Moreau JA, et al. J Am Vet Med Assoc 2002;220(11): 1664-9.

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! Dr. Lisa Powell, DACVECC

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